Comparison of methylation pattern on fatty acid binding protein 1 promoter region between A549 with HepG2 Cell lines

Lee, Jong-UK Soonchunhyang University Graduate School 2015 국내석사

ABSTRACT Comparison of methylation pattern on fatty acid binding protein 1 promoter region between A549 with HepG2 Jong-Uk Lee Department of Interdisciplinary Program in Biomedical Science Major Graduate School of Soonchunhyang University Asan, Korea (Supervised by Professor Chuch Sik Park) Backgraoud Aspirin-exacerbated respiratory disease (AERD) associated with the development of bronchoconstriction, increased secretion of mucus, infiltration of inflammatory cells in the airway wall in asthmatics following the ingestion of aspirin. AERD indicates inflammation upward trend of generation of cytokine dictated by critical mediators such as leukotrienes (LT). Fatty acid binding proteins (FABPs) play an important role of trafficking in a process of metabolism of intracellular arachidonic acid. Thus it is important to regulate FABP1 expression in a process of eicosanoid metabolism. Describe our previous report in which protein expression of FABP1 was higher in nasal polyp of patients with AERD than ATA. Recently DNA methylation is reported to be associated with gene expression. Objective The aim of this study is to investigate whether CpG methylation or demethylation on FABP1 gene promoter region affect its gene expression using A549 and HepG2 cell lines which shows different level of FABP1. Methods A549 and HepG2 epithelial cells were cultured for 4day after RNA, protein, gDNA extracted from each cell lines. gDNA was C-T conversion by bisulfate and we performed bisulfate PCR. And then, sequence analysis form Macrogen and used to alignment tool, transcription factor binding sites search from PROMO. Results FABP1was shown to have expression of mRNA, protein significantly higher in HepG2 compared with A549. We identified and obtained comparison in terms CpG locis of methylated CpG or unmethylated CpG on FABP1 gene promoter region. A549 cell line have 13 methylated, 6 unmethylated CpG sites on FABP1 gene promoter region while HepG2 cell line have 12 methylated sites, 5 unmethylated sites and 2 partial methylated CpG sites And two cell lines have different methylation patterns to FABP1 promoter region. As a result of search from PROMO for transcription binding factor, it was predicted that there will be transcription binding factor in 4 CpG sites as part of sequence such as -1181( ENKTF-1), -634(E2F-1), -373(PR B, PR A), -25 (GR-alpha, E2F-1, COUP-TF). Conclusion Our results suggest that the level of CpG methylation on promoter region of FABP1 gene could be a factor of differential FABP1 expression between hepatocyte and epithelial cells. We will further validate the effects of binding of Transcription Factor with CpG sites on FABP1 promoter region of A549 and HepG2.

Effects of Pinus densiflora needle extract on liver regeneration induced by partial hepatectomy in rat

이경석 Soonchunhyang University 2017 국내석사

Pine (Pinus densiflora) is widely distributed in Eastern Asia including Korea, China, Japan and Russia. The leaf (pine needle) has been used as a traditional medicine for gastroenteritis, hypertension, etc. Recently it has been reported that pine needle has anti-oxidative, anti-inflammatory, anti-tumor and anti-bacterial activities. The liver is an essential organ in animal since it plays a crucial role in protein synthesis, detoxification, regulation of glucose and other many metabolism. The liver has unique ability to regenerate potential after injury. Regenerative potential of the liver is well known and is widely used in physiological researches. Liver regeneration could be induced by partial hepatectomy (PH). After PH, liver regenerates via compensatory growth which does not means anatomic true-regeneration. The expanding liver does not regain its original gross anatomical structure. Remnant liver proliferates to meet metabolic needs of the organism. During liver regeneration, quiescent hepatocytes undergo one or two rounds of replication and then return to non-proliferative state. Based on physiological effects of pine needle previously mentioned, in this study, effects of pine needle extract (PNE) were investigated in regenerating rat liver. To determine the positive effects of PNE on liver regeneration induced by PH in rat, PNE was administrated to animal model and then the effects were investigated focused on protein expression which is related with cell proliferation. Juicy PNE was stored at 4℃ for 3 years before used. Rats in experimental group were provided PNE which was diluted in distilled water at 10% from 5 days before PH till sacrifice. As results, it was microscopically observed that hepatic plates were collapsed and restored during liver regeneration. Hepatocytes were divided and then hepatic structure was restored with proliferation of endothelial cells and remodelling of sinusoidal network. Vascular endothelial growth factor-A (VEGF-A) played a crucial role in this process. In serum analysis, AST and ALT activity of experimental group increased in early phase of liver regeneration. But the activities recovered within one day. In immunohistochemistry, Ki-67 which is used for biomarker to proliferation expression in hepatocyte obviously increased. It means that PNE promotes proliferation of hepatocyte. In western blot analysis, proliferating cell nuclear antigen (PCNA) expression was also relatively accelerated. PCNA expression in experimental group was peaked at 36 hrs after PH while in control group, the expression was peaked at 60 hrs after PH. In experimental group, VEGF-A expression increased quickly after PH and continued to 3 days. In rodent, proliferation of endothelial cells to restore the sinusoids occurs from 3 days till 6 days after PH. It has been reported that DNA synthesis of VEGF-A was started at 12 hrs after PH and peaked at 48 hrs. In this study, VEGF-A already increased at 12 hrs after PH. This pattern is thought to be due to the stimulation of PNE and then increased VEGF-A could accelerate the proliferation of non-parenchymal cell and restoration of sinusoid. Remodeling of sinusoid in early stage facilitates to carry nutrients and oxygen and other signal molecules for proliferation of hepatic cells. In summary, administration of PNE stimulates the expression of VEGF-A in regenerating liver and then restoration and development of sinusoidal network were promoted. These changes could promote the proliferation of hepatic cells through supplying of sufficient nutrients and oxygen. These results in early phase of liver regeneration could bring insight into the physiological events of liver and liver transplantation and would be applied to medical treatment. Further trials such as identifying of core component are asked for complete understanding the effects of PNE on regenerating liver.

(The) analysis of radiation exposure dose and risk of exposure induced cancer death to patients from conventional radiography

유동수 Soonchunhyang University 2018 국내박사

목적: Conventional Radiography 검사의 검사 횟수, 검사 대상자는 점차 증가하고 있다. 하지만 저 선량 검사이기 때문에 의료피폭에 대한 관심이 부족하다. 본 연구에서는 conventional radiography검사에서 많이 사용되는 검사에 대해 피폭 선량을 분석하였다. 대상 및 방법: 연구 방법으로는 Chest, Abdomen, Cervical Spine, Thorax Spine, Lumbar Spine, Pelvis AP 검사에서 Dose Area Product(DAP)를 후향적으로 조사하여 PCXMC 프로그램을 이용, Effective dose,와 암 발생확률, Risk of Exposure Induced cancer Death(REID)를 검사별 남녀 성별로 구하였다. DAP값은 Cervix spine lateral검사를 제외하고 성비에 따른 차이가 거의 없었고, 가장 높은 DAP값은 남녀 모두 Lumbar spine lateral 검사였다. 결과: Effective dose 에서는 chest lateral, Abdomen supine, Thoracic spine AP, Lumbar spine AP, Lumbar spine Lateral, Pelvis AP검사에서 성비에 따른 유효한 차이를 보였다 (p<0.05). 남성은 Abdomen erect 검사에서, 여성은 Lumbar spine AP 검사에서 가장 높은 유효선량 값을 보였다. 각 검사 별 평균 암 발생 확률은 남성은 Lumbar spine AP검사에서 Stomach cancer발생 확률이 높았고, 여성은 Thoracic spine lateral 검사에서 lung cancer 발생 확률이 가장 높았다. REID는 남녀 모두 Lumbar spine AP검사에서 가장 높았고, Cervical spine lateral 검사에서 가장 낮았다. 결론: Conventional radiography검사는 저 선량 검사이지만, 전리방사선을 이용하기 때문에 Linear No Threshold(LNT) 모델에 따른 Stochastic radiation risks가 있다. 본 연구를 통해 conventional radiography검사의 의료피폭 관리 방안에 대한 기초 자료를 제공 할 수 있을 것으로 사료된다. 주제어 :Radiation, PCXMC, Effective dose, Dose Area Product, Stochastic radiation risk,

골 재생을 위한 세라믹 - 하이드로 겔 기반 하이브리드 시스템 지지체의 설계 및 평가

Omar, Faruq Soonchunhyang University Graduate School 2018 국내석사

common biomaterials for bone regeneration. Beside ceramic materials, polymeric compound are promising biomaterials in tissue engineering application. Hydrogel are very flexible materials that allow a number of different properties to be targeted for different applications through that allow a different properties to be targeted for different applications, through appropriate chemical modifications. The combination of hydrogel to ceramic scaffold may overcome the existing problem as well as enhance bone formation. These materials are primarily used for helping the bone remodeling process of natural bone providing a scaffolding, intermediary mechanical support for the damaged bone and stimulating the natural regeneration process by bringing in different growth factors and stimulant and drugs. The most important morphological feature of these hybrid scaffolds is the interconnected porosity for optimal three dimensional formations. In this work, we develop a hydrogel system together with ceramic for subsequent development of bone substitute. This hybrid system has different pore size and frame thickness .All the materials showed superior biocompatibility and excellent mechanical properties. The hydrogel system also applied to injectable PMMA bone cement with better setting properties and slightly better biocompatibility. In all the materials the properties like comprehensive strength porosity characteristic frame thickness dimension, setting time etc. were measured. For the compatibility evaluation extensive in vitro investigation like MTT, cell morphology observation, cell proliferation behavior investigation was performed. For more detailed in vivo investigation was carried out by rabbit implantation for the evaluation of in physiological environment and the results showed promising performance for the hybrid ceramic-hydrogel system. Over the past few decades, bone related disorders have constantly increased. Among all pathological conditions, bone damage is one of the most common and often leads to bone fractures. This is a massive burden and it affects most of the people all over world. Furthermore, as the population ages, numbers are due to increase. To encounter the bone loss, novel biomaterials for bone fracture regeneration are constantly under development. Typically, these materials aim at favoring optimal bone integration in the scaffold, up to complete bone regeneration; this approach to regenerative medicine is also known as tissue engineering (TE). Ceramic based calcium phosphates are among the most

Liver imaging report and data system categorization of hepatocellular carcinoma using multiphasic MDCT : comparison between patients with and without moderate to severe fatty liver

김승수 Soonchunhyang University 2019 국내박사

Purpose: To compare the sensitivity of Liver Imaging Reporting and Data System (LI-RADS) v2017 for diagnosis of hepatocellular carcinoma (HCC) using multiphasic computed tomography (CT) between patients with and without moderate to severe fatty liver (MSFL). Materials and methods: This retrospective study included a total of 106 high-risk patients with 112 pathologically proven HCCs who underwent multiphasic CT. Patients were classified as MSFL (24 men, 2 women; mean age, 59.5 years [range, 38–79 years]) and non-MSFL (64 men, 16 women; mean age, 62.9 years [range, 40–89 years]) groups according to unenhanced CT liver and spleen parenchymal attenuation. Two independent radiologists assigned LI-RADS categories and accessed HCC features on CT. Sensitivities for LR-5 assignment and frequencies of HCC features were compared between the two groups. Results: Sensitivities of LR-5 assignment for diagnosing HCCs were not significantly different between MSFL and non-MSFL groups (65.4% [17/26] vs. 76.7% [66/86] for reviewer 1, P = 0.247; 73.1% [19/26] vs. 76.74% [66/86] for reviewer 2, P = 0.702). No significant differences in the frequencies of arterial hyperenhancement, washout, and capsule were observed between the two groups (96.2% [25/26] vs. 98.8% [85/86], P = 0.412; 80.8% [21/26] vs. 89.5% [77/86], P = 0.308; and 53.8% [14/26] vs. 57% [49/86], P = 0.778, respectively). Conclusion: LI-RADS v2017 using CT showed comparable sensitivity for diagnosing HCC regardless of MSFL. 본 논문은 중등도 이상의 지방간이 있는 환자와 없는 환자 사이에서 다중검출전산화단층촬영기를 이용한 간 영상 진단 및 데이터 시스템의 간세포 진단의 민감도를 비교하기 위한 연구이다. 본원에서 다중검출전산화단층촬영을 시행하고 병리학적으로 간세포암으로 진단된 106명의 고위험 환자 (112개의 간세포암)를 대상으로 하였다. 환자들은 조영증강전 전산화단층촬영 영상에서 간과 비장 실질의 감쇠에 따라 중등도이상지방간군 (남성 24명, 여성 2명, 평균 나이 59.5세 [38-79세]) 과 비중등도이상지방간군 (남성 64명, 여성 16명, 평균 나이 62.9세 [40-89세]) 으로 나뉘었다. 두 명의 독립적인 영상의학과 의사가 간 영상 진단 및 데이터 시스템의 범주를 지정하고, 전산화단층촬영 영상에서 간세포암의 주요 영상소견을 평가하였다. 두 군 사이에 간 영상 진단 및 데이터 시스템의 간세포암 진단에 대한 민감도와 간세포암 영상소견의 빈도를 비교하였다. 간세포암 진단에 대한 간 영상 진단 및 데이터 시스템의 민감도는 중등도이상지방간군과 비중증도이상지방간군 사이에 유의한 차이가 없었다. (첫번째 평가자의 경우 65.4% [17/26] 대 76.7% [66/86], P = 0.247; 두번째 평가자의 경우 73.1% [19/26] 대 76.74% [66/86], P = 0.702). 두 군 간의 동맥기 조영증강, 씻김, 그리고 캡슐의 빈도에 의미있는 차이는 없었다. (96.2% [25/26] 대 98.8% [85/86], P = 0.412; 80.8% [21/26] 대 89.5% [77/86], P = 0.308; 그리고 53.8% [14/26] 대 57% [49/86], P = 0.778). 전산화단층촬영기를 이용한 간 영상 진단 및 데이터 시스템은 중등도 이상의 지방간 여부에 상관없이 간세포암 진단에 있어 비슷한 민감도를 보였다.

Effects of 2-Hydroxypropyl-β-Cyclodextrin on Obesity-Induced Inflammation and Insulin Resistance

Park, YooNa Soonchunhyang University Graduate School 2018 국내석사

Adipose tissue macrophages (ATMs) play a key role in obesity-induced inflammation and insulin resistance. Recent studies have identified the lysosomal dysfunction in ATMs during obesity. However, the role of lysosome in the ATM-mediated inflammation and insulin resistance in obesity is not clearly elucidated. Using a 2-hydroxypropyl-β-cyclodextrin (HPβCD), chemical activator of lysosomal function, we examined whether restoration of lysosome function in ATM regulates the obesity-induced adipose tissue inflammation and insulin resistance. Diet-induced obese model was generated by feeding of high-fat diet for 15 weeks and then saline or HPβCD were administrated every other day for 2 weeks via intraperitoneal injection. Compared to vehicle-treated mice, HPβCD-treated mice showed improvement in glucose intolerance and insulin resistance, regardless of their similar body weights. Flow cytometry analysis revealed that visceral adipose tissue from HPβCD-treated mice had lower pro-inflammatory M1 ATMs and CD8+ T lymphocyte amounts, while blood leukocyte population including monocytes, neutrophils and T lymphocytes and spleen T cell populations were comparable between groups. Mechanistically, in bone marrow-derived macrophages (BMDMs) and peritoneal macrophage (pMACs), HPβCD treatment inhibited the LPS- or palminate-induced M1 activation. Upregulation of pro-inflammatory gene expression by bafilomycin A1 (Baf) and chloroquine (CQ) was also attenuated by HPβCD. Moreover, expression of Tfeb gene, master regulator of lysosomal biogenesis, was decreased in Baf-treated BMDM as well as classic M1 inducers, but its expression was restored by HPβCD. These results demonstrate that HPβCD treatment alleviates obesity-induced adipose tissue inflammation and glucose intolerance by inhibition of M1 activation and activation of lysosome through TFEB expression. Thus, restoration of lysosomal function in ATM may be a novel target for obesity-induced metabolic disease.

Upregulation of monooxygenase DBH like 1 levels in the lungs of idiopathic pulmonary fibroblast

백동규 Soonchunhyang University 2019 국내석사

특발성 폐섬유화증 (Idiopathic Pulmonary Fibrosis: IPF)은 만성염증에 의해 진행되는 간질성 폐질환으로, 지난 연구를 통해 특발성 폐섬유화증의 병인과 유전적 메커니즘에 대한 관련성이 많이 밝혀져 왔다. 그래서 우리는 이전 RNA 발현 마이크로어레이 데이터를 통해 특발성 폐섬유화증에 관련된 178개의 유전자를 선별하였다. 이 중, 구리이온의 결합과 산화 환원 효소의 활성에 관여하는 효소인 MOXD1은 특발성 폐섬유화증과의 연관성을 확인한 연구는 확인되지 않았다. 본 연구는 MOXD1와 특발성 폐섬유화증에서의 발현 양상을 알아보고자 하였다. 우리는 정상 군과 특발성 폐섬유화증 군으로 군을 나눠, RT-PCR 및 Real-time PCR을 진행한 결과 특발성 폐섬유화증 군에서 mRNA 발현의 유의한 증가를 확인하였다. 이는 이전 마이크로어레이 결과와 유의한 일치를 보였다. 동물 모델에서도 발현양상이 비슷한지 보기 위해 Bleomycin을 쥐에 주입하여 특발성 폐섬유화증 모델을 만들어 protein 발현량을 보았는데, Western blot, Immunohistochemical stain에서 모두, sham 군에 비해 특발성 폐섬유화증 모델 군에서 MOXD1 발현량이 증가하는 것을 확인 하였다. 그리고 다른 간질성 폐질환 군으로 각각 비 특이성 간질성 폐질환군 (nonspecific intersititial pneumonia: NSIP), 과민성 폐장염군 (Hypersensitivity pneumonitis: HP), 유육종증군 (Sarcoidosis)의 기관지 폐포세척액을 추가하여 ELISA을 측정했다. 다른 군들보다 특발성 폐섬유화증 군에서 유의하게 MOXD1의 발현량이 증가한 점을 확인하였다. 이를 통해, 정상군 및 특발성 폐섬유화증군과의 ROC curve를 대조하였을 때, Area under ROC curve(AUC): 0.716, Specificity: 86.7 %, Sensitivity: 61.2 %를 확인하였고, 다른 간질성 폐질환 군 및 특발성 폐섬유화증군과의 ROC curve를 대조하였을 때, AUC: 0.722, Specificity: 86.7 %, Sensitivity: 62.5 %를 확인하였다. 특발성 폐섬유화증군의 임상적 특징에 따라 그룹을 나눈 Gap stage I, II, III군, 흡연여부에 따른 흡연, 금연, 비 흡연 군, 그리고 남성, 여성 군으로 나눠 MOXD1의 발현량을 확인하였을 때에는 유의한 차이를 보이지 않았다. 본 연구의 제한점으로는 NSIP, HP, Sarcoidosis군의 개체 수가 소수이며, 암이 발생한 폐에서 유래된 섬유아세포의 유전자 발현이 정상 폐에서 유래된 섬유아세포와 다를 수 있다는 점이 있다. 해당 결과를 보았을 때, MOXD1는 특발성 폐섬유화증의 발달과 연관성 및 바이오마커로서의 기능을 보일 것으로 판단된다. Background: Our previous transcriptome study of cultured fibroblasts identified 178 genes that were differentially expressed by idiopathic pulmonary fibrosis (IPF) fibroblasts compared with controls. Among them, monooxygenase DBH like 1 (MOXD1) was reported increased expression in non-cultured fibroblast from Emblom-Callahan MC's study. However, the functional importance of MOXD1 has not been evaluated in IPF. Methods: MOXD1 mRNA expression was measured using real time PCR and RT-PCR. And protein expression was measured uising Western blot. For animal IPF model, mouse were sensitized intratracheal injection using Bleomycin. The protein concentration was measured by enzyme-linked immunosorbent assay in bronchoalveolar lavage (BAL) fluids obtained from normal control (n=30) and from patients with idiopathic pulmonary fibroblast (n=80), non-specific interstitial pneumonia (NSIP) (n=10), hypersensitivity pneumonitis(HP) (n=10), and sarcoidosis (n=10). Results: MOXD1 mRNA levels were significantly higher in IPF-fibroblast (n=14) than those in controls (n=10). In animal models, IPF group showed higher Moxd1 protein levels than sham group. MOXD1 protein levels were significantly higher in the IPF patients than those in the NC [0.84(0.44-1.52 ng/mL) vs. [0.88(0.33-2.45 ng/mL), p=0.000092] those in the NSIP [0.09(0.01-0.19 ng/mL), p=0.000177], p=0.218110] and those in sarcoidosis patients [0.28(0.19-0.44 ng/mL), p=0.003789], but there were no difference to compared HP [0.61(0.27-1.3 ng/mL), p=0.653]. Cut-off values of 3.9 ng/mL and 3.73 possessed 71.6 % and 73.7 % accuracy for the discrimination of IPF from NC and interstitial lung diseases (ILDs), respectively. IPF subjects with MOXD1 levels >5.968 ng/mL showed shorter survival compared to those with lower levels (p=0.00026). In addition, MOXD1 gene expression was significantly increased in fibroblasts and lung tissue from the patients with IPF. Conclusion: MOXD1 may be associated with the development of IPF. Futhermore, the MOXD1 in BAL fluids may be useful for differentiating IPF from other ILDs.

Combined vitrectomy with macular buckling in high myopic eyes with macular hole retinal detachment : a pilot study of a novel snail-tipped exoplant

선해정 Soonchunhyang University 2019 국내박사

PURPOSE: To evaluate the efficacy of a novel snail-tipped exoplant for macular buckling(MB) combined with vitrectomy in high myopic eyes with macular hole retinal detachment (MHRD). METHODS: A novel exoplant was simply prepared with a 5x3 mm silicone sponge strengthened in the center with a malleable titanium plate. One end was bent to make a rolled tip like a snail shell to be placed under the macula. Combined vitrectomy with MB using this exoplant was performed in eight consecutive cases of MHRD. The long arm of the exoplant was manipulated manually to fit the curvature of the eyeball and the length was trimmed appropriately after scleral suturing of the exoplant. RESULTS: Retinal reattachment was achieved in all cases (100%) and macular hole closure was confirmed in 6 eyes (75%). The mean best-corrected visual acuity improved from 1.53 ± 0.73 LogMAR preoperatively to 1.14 ± 0.59 LogMAR to postoperatively (p = 0.063). The mean pre- and postoperative AL was 28.44 ± 1.86 mm and 27.60 ± 1.83 mm, respectively (p = 0.016). The mean follow-up period was 15.4 months and no buckle related complications such as diplopia, infection or exposure of the exoplant was noticed during the period. Recurrence of MHRD occurred in none of the cases. CONCLUSION: Pilot results of the snail-tipped exoplant for MB was effective for retinal reattachment in MHRD. This exoplant could easily be prepared with readily available materials in the operating room and it was well tolerated with favorable anatomic results in high myopic eyes. Further studies of increased number of patients with long-term follow-up will be necessary. 목적: 황반원공에 의해 발생한 망막박리가 있는 고도근시안에서 달팽이관 모양의 외부돌륭물질을 이용해 황반돌륭술과 유리체절제술을 동시에 시행하여 그 효과를 알아보고자 하였다. 방법: 외부돌륭물질은 5x3 mm 실리콘 스펀지 중심에 가단성이 있는 티타늄 판을 삽입하여 한 쪽 끝을 달팽이관 모양으로 말아서 준비하였다. 달팽이관의 형태로 감은 부분이 황반부에 위치하도록 하여 돌륭효과를 증대시켰고 황반원공에 의한 망막박리가 있는 8명의 고도근시 환자 8안에서 유리체절제술과 동시에 이 외부돌륭물질을 이용하여 황반돌륭술을 시행하였다. 외부돌륭물질의 긴 쪽 끝은 안구의 곡률에 맞도록 구부려서 상이측 공막에 그 끝을 고정하였고, 봉합 후 외부돌륭물질의 남는 부분은 티타늄 판이 실리콘 스펀지 밖으로 노출되지 않도록 잘라내었다. 결과: 8안 모두에서 망막의 재유착이 이루어졌고 (100%) 황반원공의 폐쇄는 6안에서 확인되었다 (75%). 평균 최대교정시력은 수술 전 1.53 ± 0.73 LogMAR에서 수술 후 1.14 ± 0.59 LogMAR로 호전되었다 (p = 0.063). 평균 안축장 변화는 술 전 28.44 ± 1.86 mm에서 술 후 27.60 ± 1.83 mm로 감소를 보였다 (p = 0.016). 술 후 평균 경과관찰 기간은 15.4 개월이었고 이 기간 중 복시, 감염 또는 돌륭물질의 노출 등 외부돌륭물질과 관련된 합병증은 발생하지 않았고 망막의 재박리도 관찰되지 않았다. 결론: 달팽이관 모양의 외부돌륭물질을 사용하여 황반돌륭술을 시행한 예비연구의 결과 망막의 재유착을 효과적으로 유지할 수 있었다. 본 외부돌륭물질은 수술실에서 쉽게 구할 수 있는 재료로 제작과정이 간단하고, 고도근시안에서 좋은 해부학적 수술결과를 이룰 수 있었다. 본 연구의 장기적인 효과와 합병증에 대해서는 추후 장기적 경과 관찰과 추가적인 비교연구가 필요할 것이다.

Function of Sinapic acid on induction of thermogenic signature in brown adipocyte

Hossain, Monir Soonchunhyang University Graduate School 2019 국내석사

Obesity is now a worldwide epidemic and categorizes as one of the chronic diseases by World Health Organization in the 21st century. Lipid accumulation in white adipose tissue is the key contributor to the obesity and orchestrates numerous metabolic health problems such as type 2 diabetes, hypertension, atherosclerosis, and cancer. Nonetheless, the prevention and treatment of obesity are still inadequate. Recently, scientists found that brown adipose tissue (BAT) in adult humans has functions that are diametrically opposite to those of white adipose tissue and that BAT holds promise for a new strategy to counteract obesity. Findings have revealed that increase in the mass of brown adipose tissue or activating its function can reduce body mass in rodent models. While white adipose tissue (WAT) contributes to obesity by storing triglycerides, brown adipose tissue (BAT) dissipates energy in the form of heat. In this study, we evaluated the potential of sinapic acid (SA) to promote the thermogenic program and lipolysis in BAT. SA treatment of brown adipocytes induced the expression of brown-adipocyte activation–related genes such as Ucp1, Pgc-1α, and Prdm16 and mitochondrial biogenesis-related genes including Nrf1. Additionally, we observed that SA treatment can reduce the expression of adipogenesis inhibiting factors PREF, WNT10a, and WNT10b. Furthermore, structural analysis and western blot revealed that SA competitively inhibits pan-PKA inhibitor, H89 and can upregulate protein kinase A (PKA) phosphorylation. SA binds to the adenosine triphosphate (ATP) site on the PKA catalytic subunit where H89 binds specifically. It is confirmed by PKA-cat-α1 gene–silencing experiments that SA can activate the thermogenic program via a mechanism involving PKA and cyclic AMP response element–binding protein (CREB) signaling. Moreover, SA treatment promotes lipolysis via a PKA/p38-mediated pathway. Our findings may allow us to open a new avenue of strategies against obesity and need further investigation.

Predictors of increase in false lumen volume after stent-grafting in patient with type B aortic dissection

김태훈 Soonchunhyang University 2014 국내박사

B형 대동맥 박리 환자에서 인조혈관스텐트(stent-graft) 시술 후 가강(false lumen) 용적 증가의 예측인자 김태훈 순천향대학교 대학원 의학과 (지도교수 현민수) 목적: Stanford B형 대동맥박리 환자에서 인조혈관스텐트 시술 후 가강(false lumen)의 감소는 좋은 예후의 지표로 알려져 있다. 저자는 시술 후 가강 용적 증가의 예측인자를 평가하고자 하였다. 방법: B형 대동맥박리로 인조혈관스텐트 시술 후 전산화 단층 촬영(Computed tomography, CT)상 진강(true lumen)과 가강이 분리된 상태이며 일차 열공(primary tear)이 성공적으로 차단되고, 시술관련 합병증이 없는 환자 중 12개월 후의 CT를 시행한 환자를 대상으로 후향적으로 분석하였다. CT상 가강의 용적이 증가한 군(1군)과 증가 하지 않은 군(2군)에 대하여 인구학적 지표, 위험인자와 동반질환, 대동맥 박리의 유병기간 및 CT를 통한 열공의 위치, 개수, 박리의 길이, 진강 및 가강의 면적, 용적 등을 비교하였다. 결과: 총 38명의 환자 가운데 남자는 25명, 평균나이는 60 ± 12세였고 가강이 증가한 1군은 총 11명(28.9%)이었다. 1군에서 관상동맥 질환의 동반이 많았으나(36.5% vs. 7.4%, p=0.047) 그 이외의 성별, 나이, 위험인자 및 동반질환 여부는 양 군간 차이가 없었다. 시술 전 CT상 최대 가강 면적은 1군에서 유의하게 컸다(21.0 ± 11.4 cm2 vs. 12.6 ± 6.6 cm2, p=0.041). 이는 가강 용적 증가의 독립적 예측 변수였고[승산 비(odds ratio, OR)=1.3, 95% 신뢰구간(confidence interval, CI)=1.02~1.70, p=0.031], 16.1cm2을 절단값(cut off value)으로 그보다 큰 경우 위험성이 증가했다[곡선하면적(area under the curve, AUC)= 0.76, 95% CI= 0.60~0.92, 민감도= 63%, 특이도= 81.5%, p=0.012]. 결론: B형 대동맥박리 환자에서 시술 전 CT상 최대 가강 면적이 클수록 인조혈관스텐트 시술 후 가강 용적이 증가했다. 이는 시술 후 가강 용적 증가의 예측 인자로 사료된다.